title: PDGF receptor activation induces p120-catenin phosphorylation at serine 879 via a PKCalpha-dependent pathway.
abstract: p120-catenin (p120) is required for cadherin stability and is thought to have a central role in modulating cell-cell adhesion. Several lines of evidence suggest that S/T phosphorylation may regulate p120 activity, but the upstream kinases involved have not been established, nor has a discreet measurable function been assigned to an individual site. To approach these issues, we have generated p120 phospho-specific monoclonal antibodies to several individual phosphorylation sites and are using them to pinpoint upstream kinases and signaling pathways that control p120 activity. Protein Kinase C (PKC) has been implicated as a signaling intermediate in several cadherin-associated cellular activities. Signaling events that activate PKC induce rapid phosphorylation at p120 Serine 879 (S879), suggesting that p120 activity is regulated, in part, by one or more PKC isoforms. Here, we find that physiologic activation of a G-protein coupled receptor (i.e., endothelin receptor), as well as several Receptor Tyrosine Kinases, induce rapid and robust p120 phosphorylation at S879, suggesting that these pathways crosstalk to cadherin complexes via p120. Using Va2 cells and PDGF stimulation, we show for the first time that PDGFR-mediated phosphorylation at this site is dependent on PKCalpha, a conventional PKC isoform implicated previously in disruption of adherens junctions.
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Meredith V
authors.initials: MV
authors.lastname: Brown
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Burnett
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Denning
authors.forename: Albert B
authors.initials: AB
authors.lastname: Reynolds
mesh_terms: D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D015815:Cell Adhesion Molecules; D007527:Isoenzymes; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D043562:Receptors, G-Protein-Coupled; D010768:Phosphoserine; D017479:Receptors, Platelet-Derived Growth Factor; D051571:Protein Kinase C-alpha; D000095002:Delta Catenin; C000722347:CTNND1 protein, human